A study involving PC-3 cancer cells and novel carbamate gemini surfactants: Is zeta potential the key to control adhesion to cells?

Liposome surface potential effect on cellular uptake and cytotoxicity is evaluated using liposomes, modified with cationic lipid DOTAP, a series of cationic gemini surfactants with two carbamate fragments, and an amphiphilic peptide SSRGD. The surfactants used are novel representatives of the gemini family with improved self-assembling activity coupled with potential biodegradable properties and displayed increasing antibacterial activity and cytotoxicity with the shortening of hydrophobic alkyl tails. The longest alkyl tail surfactant, 14-6-14(Et), was the most biocompatible of the series, which was chosen for liposome modification. Prepared liposomes of various compositions are characterized from morphological and physicochemical standpoints in order to optimize their biocompatibility and stability. The carbamate gemini surfactants were also twice as effective at providing positive charge to liposomes and less toxic compared to DOTAP. On their own, carbamate surfactants were able to increase cellular uptake of liposomes by 190%. The mixed composition of 14-6-14(Et) surfactant and SSRGD amphiphilic peptide was the most readily absorbed formulation among different tested neutral, cationic and RGD-modified liposomes. The comparison between the cellular uptake promotion is conducted as to what is the most selective and efficient approach to enhance lipid nanoparticle uptake by cancerous cells.